The purpose of this project is to determine the natural course of renal disease in type 2 diabetes mellitus in the Pima Indians and to identify the underlying pathogenetic mechanisms involved in the initiation and progression of renal disease in this type of diabetes. This project, in part, represents an extension of work previously reported as Project Number Z01 DK 69037. Glomerular function was measured initially over a 4-year period in 194 Pima Indians selected to represent stages in the development and progression of diabetic renal disease. Eighty-six of these subjects had type 2 diabetes and micro- or macroalbuminuria. Subjects underwent serial determinations of albuminuria and GFR. Many of these subjects continue to be followed and they have accumulated over 15 years of data on glomerular hemodynamic function in type 2 diabetes. Many of these subjects have also had kidney biopsies. Our efforts in the coming year will focus on the pathobiology of kidney disease. We wish to identify, in particular, the role of the glomerular podocyte in the development and progression of diabetic kidney disease.